PhysioNet, established in 1999 as the NIH-sponsored Research Resource for Complex Physiologic Signals, has attained a preeminent status among data and software resources in biomedicine. Its data archive, PhysioBank, was the first, and remains the world's largest, most comprehensive and most widely used repository of time-varying physiologic signals. Its software collection, PhysioToolkit, supports exploration and quantitative analyses of PhysioBank and similar data with a wide range of well-documented, rigorously tested open-source software that can be run on any platform. PhysioNet's team of researchers leverages results of other funded projects to drive the creation and enrichment of: Data collections that provide increasingly comprehensive, multifaceted views of pathophysiology over long time intervals, such as the MIMIC II (Multiparameter Monitoring in Intensive Care) Database of critical care patients; Analytic methods that lead to more timely and accurate diagnoses of major public health problem (such as life-threatening cardiac arrhythmias, infant apneas and seizures), and elucidation of dynamical changes associated with disease and aging (such as cardiopulmonary interactions during sleep disordered breathing syndromes); User interfaces, reference materials and services that add value and improve accessibility to PhysioNet's data and software (such as PhysioNetWorks, a virtual laboratory for data sharing). Impact: Cited in The White House Fact Sheet on Big Data Across the Federal Government (March 29, 2012), PhysioNet is a proven enabler and accelerator of innovative research by investigators with a diverse range of interests, working on projects made possible by data that are inaccessible otherwise. PhysioNet's world- wide, growing community of over 40,000 researchers, clinicians, educators, students, and medical instrument and software developers, retrieve about 700 GB of data per day. By providing free access to its unique and wide-ranging data and software collections, PhysioNet enables studies that currently result in an impressive average of nearly 130 new publications per month by academic, clinical, and industry-affiliated researchers worldwide. Specific aims: For the next 5 years we aim to: 1. Sustain and enhance PhysioNet's impact with new technology and data; 2. Drive relevant innovation through a vigorous research program on complex physiologic signals; 3. Stimulate and support a growing community of investigators.